Study record
A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c
Zempo H, Kim SJ, Fuku N et al. · Aging (Albany NY) · 2021
What this study reported
Reported that males but not females carrying the C allele of the m.1382A>C variant, which produces K14Q-MOTS-c, had a higher prevalence of type 2 diabetes, with the association concentrated in men in the lowest physical-activity tertile. In high-fat-fed male mice, administered MOTS-c was associated with lower weight and improved glucose tolerance while K14Q-MOTS-c was not, and K14Q-MOTS-c showed diminished insulin-sensitising activity in cells.
Limitations
Genetic associations are observational and restricted to East Asian cohorts, the physical-activity interaction is based on self-reported tertiles, and the supporting animal work used male mice of a single strain with female mice reported as unaffected.
Study record
| Study model | Human observational |
|---|---|
| Substance studied | SeveralMore than one of these is central to the paper (common for reviews). |
| Species | human, mouse |
| System studied | Meta-analysis of three Asian cohorts genotyped for m.1382A>C, plus high-fat-fed mice given MOTS-c or K14Q-MOTS-c and cell experiments |
| Population | adults from three Japanese and multi-ethnic cohorts (J-MICC, MEC, TMM) |
| Design | Genetic association meta-analysis with supporting controlled animal and cell experiments |
| Sample size as reported | 27,527 participants across three cohorts |
| Control group | A-allele carriers within the same cohorts; vehicle and K14Q-MOTS-c comparison groups in mice |
| Route (data field only) | Not reported |
| Endpoints measured | type 2 diabetes prevalence; body weight; glucose tolerance; insulin sensitisation |
| Pathways measured | Insulin & glucose handling · AKT / mTOR / FOXO |
| Research areas | Metabolic · Exercise · Aging |
| Evidence tier | B — Other human study |
| Publication types | Journal Article, Research Support, Non-U.S. Gov't |
Appraisal
Each dimension is recorded separately and never combined into a single score. A study can be well controlled and still tell you little about people.
- Relevance to MOTS-c
- Direct
- Model applicability
- Human
- Sample size
- Adequate
- Controls
- Appropriate
- Outcome validity
- Clinical outcome
- Support for its own conclusion
- Moderate
Provenance
- Bibliographic fields retrieved from PubMed E-utilities efetch (title, journal, date, authors, DOI) on 2026-11-11.
- Annotated from the published abstract.
- Editorial review: approved (2026-11-11).
- Classification follows the site methodology; the record describes the study, not what MOTS-c does in people.